Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis (iSite)
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|ClinicalTrials.gov Identifier: NCT03779139|
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : September 21, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Chronic Pancreatitis Diabetes Mellitus Islet Cell Transplantation||Procedure: Intrahepatic islets and islets in the omental pouch Procedure: Intrahepatic islets alone Other: Normal Volunteers||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Trial of Intra-Portal Alone Versus Intra- and Extra-Portal Transplantation of Pancreatic Islets After Total Pancreatectomy for Chronic Pancreatitis|
|Actual Study Start Date :||August 1, 2019|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
|Active Comparator: Intrahepatic islets alone||
Procedure: Intrahepatic islets alone
This is the standard of care procedure. Patients with islet harvest of >5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to all islets autotransplanted intrahepatically via the intraportal route.
|Experimental: Intrahepatic and omental pouch islets||
Procedure: Intrahepatic islets and islets in the omental pouch
Patients with islet harvest of >5000 islet equivalents per kg body weight will be randomized in a 1:1 ratio to 4000 IEq/kg delivered via intraportal route and the remainder implanted into a constructed omental pouch.
|Sham Comparator: Normal Volunteers||
Other: Normal Volunteers
These individuals will undergo metabolic testing as well as islet cell function testing.
- Portal vein thrombosis [ Time Frame: Post operative day 4 or 5. ]Portal vein thrombosis is associated with higher tissue volume infused into the portal vein and higher portal pressures and is assessed using abdominal ultrasound.
- Clavien-Dindo classification of surgical complications [ Time Frame: Within 30 days of surgery ]Grades surgical complications based on the level of treatment necessary to treat the complication.
- Mixed Meal Tolerance Test [ Time Frame: 1 year ]Patient is given Boost HP (6cc/kg), ingested 5 minutes after t=0 blood draw. Blood is drawn every half hour for 2 hours.
- Intravenous Glucose tolerance test [ Time Frame: 1 year ]Patients are given a bolus of 0.2mg/kg of dextrose at t=0. Blood samples will be drawn at t=-10,-5,-1,2,3,4,5,7 and 10 minutes
- Glucose potentiated arginine stimulation [ Time Frame: 1 year ]
Starting immediately after glucose tolerance test (time t=10 minutes), 20% dextrose will be infused to maintain a glucose ~230mg/dL until test is completed. Glucose levels are measured every 5 minutes to maintain glucose in the target range after 40 minutes of continuous 20% dextrose infusion, After 40 minutes of continuous D20% infusion, baseline samples for glucose, insulin, and C-peptide are drawn (three samples over 10 minutes), a bolus of 5 grams arginine is given (at time 55 minutes), and samples for glucose, insulin, and C-peptide are taken at 2, 3, 4, and 5 minutes after
the arginine bolus.
- Hypoglycemic clamp [ Time Frame: 1 year ]A stepped hypoglycemic clamp protocol with variable glucose infusion rates will be performed to achieve 45 min glucose plateaus at 70, 60, and 50 mg/dl.Glucagon responses will be calculated by subtracting the mean of the three baseline values observed prior to the clamp from glucagon levels observed at 70, 60, and 50 mg/dl glucose nadirs during the clamp
- Continuous glucose monitoring [ Time Frame: 1 year ]3 days of CGM monitoring at one year will be obtained for mean glucose,standard deviation, and percent of time in hypo- and hyperglycemia
- Hemoglobin A1c levels [ Time Frame: 1 year ]Measure of average glucose levels over last several weeks
- Insulin Use [ Time Frame: 1 year ]calculated as units/kg/day, will be assessed from glucose and insulin diaries maintained by patients for 14 days, overlapping with day 90
- Hypoglycemic episodes [ Time Frame: 1 year ]All severe hypoglycemic events will be recorded. This is defined based on American Diabetes Association criteria as a hypoglycemic episode <54 mg/dL or (if not measured) associated with prompt recovery upon administration of glucose in which a patient is mentally or physically incapacitated and requires assistance from another person to treat the hypoglycemia.
- Clarke score [ Time Frame: 1 year ]is determined from eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia; it evaluates symptomatic responses to hypoglycemia. A score of 4 or greater suggests impaired awareness of hypoglycemia
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 68 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- Age 18-68
- Scheduled for total pancreatectomy and IAT at U of MN. All patients who are approved for pancreatectomy and IAT at U of MN are reviewed by a multi-disciplinary committee including surgeons, gastroenterologists specializing in pancreatic disease, a pain specialist psychologist, and endocrinologist to confirm the diagnosis of chronic pancreatitis and candidate suitability for surgery.
- Able to provide informed consent
- Pre-Existing diabetes mellitus fasting blood glucose>115mg/dl, or hemoglobin A1c level >6.0% because these are all evidence of inadequate beta-cello mass.
- Use of any of the following treatments in the 30 days prior to enrollment: insulin, metformin, sulfonylureas, glinides, thiazolidinediones, GLP-1 agonists, DPP-4 inhibitors, or amylin.
- ALT or AST>2.5 times the upper limit of normal (ULN). Bilirubin>ULN, unless due to benign diagnosis such as Gilbert's.
- Any of the following hematologic abnormalities: server anemia (hemoglobin <10 g/dL), thrombocytopenia (<150/mm3), or neutropenia(<1.0 x 109/L).
- Current use or expected use of oral or injected corticosteroids, or any mediation likely to affect glucose tolerance. However, use of hydrocortisone for physiologic replacement, or use of any topical, inhaled or intranasal glucocorticoid is permitted.
- Current or expected use of any other immunosuppressive agent.
- Known coagulopathy, or need for anticoagulant therapy preoperatively (coumadin, enoxaparin), or any history of pulmonary embolism.
- For females, plans to become pregnant or unwillingness to use birth control for the study duration.
- Inability to comply with the study protocol.
- Untreated psychiatric illness that may interfere with ability to give informed consent, or other developmental delay or neurocognitive disorder that impairs with a patient's ability to consent on their own behalf.
- Any other medical condition that , in the opinion of the investigator, may interfere wit the patient's ability to successfully and safely complete the trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03779139
|Contact: Kristine Mulieremail@example.com|
|United States, Minnesota|
|University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Greg Beilman 612-625-7911 firstname.lastname@example.org|
|Principal Investigator:||Greg Beilman, MD||University of Minnesota, Department of Surgery|
|Responsible Party:||University of Minnesota|
|Other Study ID Numbers:||
|First Posted:||December 19, 2018 Key Record Dates|
|Last Update Posted:||September 21, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
total pancreatectomy with islet autotransplant
Digestive System Diseases